Colchicine prevents atrial fibrillation promotion by inhibiting IL-1β-induced IL-6 release and atrial fibrosis in the rat sterile pericarditis model.
秋水仙碱在大鼠无菌心包炎模型中通过抑制 il-1 β 诱导的 IL-6 释放和心房纤维化防止房颤促进。
- 作者列表："Wu Q","Liu H","Liao J","Zhao N","Tse G","Han B","Chen L","Huang Z","Du Y
:A few clinical trials have recently reported the potential effect of colchicine in preventing post-operative atrial fibrillation (POAF) and early atrial fibrillation (AF) recurrence after catheter pulmonary vein isolation. However, the molecular mechanisms through which colchicine inhibits AF remain unclear. We aim to assess the anti-AF effect of colchicine in the rat sterile pericarditis (SP) model and to investigate its molecular mechanisms. SP was induced in Sprague-Dawley rats by the epicardial application of sterile talc. Treatment with colchicine or vehicle began 1 d before pericardiotomy. AF was induced by transesophageal burst pacing on day 3 after surgery. Treatment with colchicine reduced the duration of AF and the probability of induction of AF in SP rats. The dose of 0.5 mg kg-1·day-1 had the best effect. Such treatment also reduced neutrophil infiltration, the mRNA expression of IL-6, TGF-β, and TNF-α, atrial fibrosis, fibrosis related genes, and signal molecules (STAT3, P38, and AKT). Meanwhile, the release of IL-1β (4-24 h) and IL-6 (4-72 h) in atria after surgery was significantly inhibited by colchicine. In cultured rat cardiac fibroblasts, colchicine treatment inhibited IL-1β-induced expression of IL-6, which was accompanied by significantly decreased phosphorylation of P38, AKT, JNK, and NFκB. Interestingly, the supplementation of IL-6 abolished the anti-AF effect of colchicine in SP rats. Colchicine prevents AF in SP rats through the inhibition of IL-1β-induced IL-6 release and subsequent atrial fibrosis. However, further studies are required to investigate whether colchicine inhibits POAF through other mechanisms.
: 最近一些临床试验报道了秋水仙碱在预防导管肺静脉隔离术后心房颤动 (POAF) 和早期心房颤动 (AF) 复发中的潜在作用。然而，秋水仙碱抑制 AF 的分子机制仍不清楚。我们旨在评估秋水仙碱在大鼠无菌心包炎 (SP) 模型中的抗 AF 作用，并探讨其分子机制。Sprague-Dawley 大鼠心外膜应用无菌滑石粉诱导 SP。在心包切开术前 1 d 开始秋水仙碱或溶剂治疗。术后第 3 天经食管爆裂起搏诱发房颤。秋水仙碱治疗减少了 SP 大鼠 AF 的持续时间和诱发 AF 的概率。0.5 mg · kg-1 · d-1 的剂量效果最好。这种治疗还减少了中性粒细胞浸润、 IL-6 、 TGF-β 和 TNF-α 的 mRNA 表达、心房纤维化、纤维化相关基因和信号分子 (STAT3 、 P38 、和 AKT)。同时，秋水仙碱可明显抑制术后心房内 il-1 β (4-24 h) 和 IL-6 (4-72 h) 的释放。在培养的大鼠心脏成纤维细胞中，秋水仙碱处理抑制 il-1 β 诱导的 IL-6 表达，伴随着 P38 、 AKT 、 JNK 和 nf κ b 磷酸化的显著降低。有趣的是，补充 IL-6 消除了秋水仙碱对 SP 大鼠的抗 AF 作用。秋水仙碱通过抑制 il-1 β 诱导的房颤释放和随后的心房纤维化，预防 SP 大鼠 IL-6。然而，需要进一步的研究来调查秋水仙碱是否通过其他机制抑制 POAF。
METHODS:AIMS:Pulmonary vein isolation (PVI) using ablation index (AI) incorporates stability, contact force (CF), time, and power. The CLOSE protocol combines AI and ≤6 mm interlesion distance. Safety concerns are raised about surround flow ablation catheters (STSF). To compare safety and effectiveness of an atrial fibrillation (AF) ablation strategy using AI vs. CLOSE protocol using STSF.,METHODS AND RESULTS:First cluster was treated using AI and second cluster using CLOSE. Procedural data, safety, and recurrence of any atrial tachycardia (AT) or AF >30 s were collected prospectively. All Classes 1c and III anti-arrhythmic drugs (AAD) were stopped after the blanking period. In total, all 215 consecutive patients [AI: 121 (paroxysmal: n = 97), CLOSE: n = 94 (paroxysmal: n = 74)] were included. Pulmonary vein isolation was reached in all in similar procedure duration (CLOSE: 107 ± 25 vs. AI: 102 ± 24 min; P = 0.1) and similar radiofrequency time (CLOSE: 36 ± 11 vs. AI: 37 ± 8 min; P = 0.4) but first pass isolation was higher in CLOSE vs. AI [left veins: 90% vs. 80%; P < 0.05 and right veins: 84% vs. 73%; P < 0.05]. Twelve-month off-AAD freedom of AF/AT was higher in CLOSE vs. AI [79% (paroxysmal: 85%) vs. 64% (paroxysmal: 68%); P < 0.05]. Only four patients (2%) without recurrence were on AAD during follow-up. Major complications were similar (CLOSE: 2.1% vs. AI: 2.5%; P = 0.87).,CONCLUSION:The CLOSE protocol is more effective than a PVI approach solely using AI, especially in paroxysmal AF. In this off-AAD study, 79% of patients were free from AF/AT during 12-month follow-up. The STSF catheter appears to be safe using conventional CLOSE targets.
METHODS:OBJECTIVE:To investigate the role of driver mechanism and the effect of electrogram dispersion-guided driver mapping and ablation in atrial fibrillation (AF) at different stages of progression.,METHODS:A total of 256 consecutive patients with AF who had undergone pulmonary vein isolation (PVI) plus driver ablation or conventional ablation were divided into three groups: paroxysmal atrial fibrillation (PAF; group A, n = 51); persistent atrial fibrillation (PsAF; group B, n = 38); and long standing-persistent atrial fibrillation (LS-PsAF; group C, n = 39). PVI was performed with the guidance of the ablation index. The electrogram dispersion was analyzed for driver mapping.,RESULTS:The most prominent driver regions were at roof (28.0%), posterior wall (17.6%), and bottom (21.3%). From patients with PAF to those with PsAF and LS-PsAF: the complexity of extra-pulmonary vein (PV) drivers including distribution, mean number, and area of dispersion region increased (P < .001). Patients who underwent driver ablation vs conventional ablation had higher procedural AF termination rate (76.6% vs 28.1%; P < .001). With AF progression, the termination rate gradually decreased from group A to group C, and the role of PVI in AF termination was also gradually weakened from group A to group C (39.6%, 7.4%, and 4.3%; P < .001) in patients with driver ablation. At the end of the follow-up, the rate of sinus rhythm maintenance was higher in patients with driver ablation than those with conventional ablation (89.1% vs 70.3%; P < .001).,CONCLUSION:The formation of extra-PV drivers provides an important mechanism for AF maintenance with their complexity increasing with AF progression. Electrogram dispersion-guided driver ablation appears to be an efficient adjunctive approach to PVI for AF treatment.
METHODS:PURPOSE:Whether or not pulmonary vein isolation (PVI) plus left atrial posterior wall isolation (PWI) using contact force (CF) sensing improves the ablation outcome for persistent atrial fibrillation (AF) is unclear. This study compared the outcome of PVI plus PWI and additional non-PV trigger ablation for persistent AF with/without CF sensing. METHODS:This retrospective cohort study analyzed 148 propensity score-matched persistent AF patients (median duration of persistent AF, 8 months (interquartile range, 3-24 months); left atrial diameter, 43 ± 7 mm) undergoing PVI plus PWI and ablation of non-PV triggers provoked by high-dose isoproterenol, including 74 with CF-sensing catheters (CF group) and 74 with conventional catheters (non-CF group). PVI plus PWI with no additional ablation but cavotricuspid isthmus ablation was performed without non-PV triggers in 48 CF patients (65%) and 54 non-CF patients (73%) (P = 0.38). In all other patients, we performed additional ablation of provoked non-PV triggers. RESULTS:The Kaplan-Meier estimate of the rate of freedom from atrial tachyarrhythmia recurrence of antiarrhythmic drugs at 12 months after the single procedure was higher in the CF group than in the non-CF group (85 vs. 70%, log-rank P = 0.030). A multivariable analysis revealed that using CF sensing and non-inducibility of AF from a non-PV trigger after PVI and PWI were significantly associated with a reduced rate of atrial tachyarrhythmia recurrence. CONCLUSIONS:Compared with non-CF sensing, PVI plus PWI and additional non-PV trigger ablation using CF-sensing catheters for persistent AF can reduce the rate of atrial tachyarrhythmia recurrence.